Proliferative diseases, such as cancer, are characterised by uncontrolled and unregulated cellular proliferation. Precisely what causes a cell to proliferate in an uncontrolled and unregulated manner has been the focus of intense research over recent decades.
Aurora kinases, a family of three serine-threonine kinases designated as A, B, and C, play key and distinct roles in different stages of mitosis.1-3 At the early stages of mitosis, Aurora-A forms a complex with the targeting protein for Xklp2 (TPX2) that regulates centrosome maturation and mitotic spindle assembly.4,5 Aurora-B forms complexes with the inner centromere protein (INCENP), survivin and borealin thereby regulating chromosome condensation, chromosome alignment, mitotic checkpoint and cytokinesis.6-9 Over expression of Aurora-A and Aurora-B has been reported in a wide range of human malignancies including breast, colorectal, ovarian, glioma, thyroid carcinoma, and seminoma.10-16 The function of Aurora-C during mitosis is less well understood. However, high expression of Aurora-C has been reported in the testis.17, 18 
In recent years, small-molecule targeting of Aurora kinases has been become a common strategy for the discovery of new cancer chemotherapeutics, and a number of structurally diverse inhibitors of Aurora activity have been reported,18-20 including 1 (VX-680 (MK-0457)),21 2 (AZD1152)22, 3 (PHA-739358),23, 24 and 4 (AMG 900)25 (see below).

However, there remains a need to identify further therapeutic agents capable of inhibiting Aurora kinase activity.
International Patent Publication Nos. WO2007/072017 and WO2009/001021 both disclose a series of imidazo[4,5-b]pyridine derivatives that function as inhibitors of Aurora kinase activity, and which are therefore potentially useful therapeutic agents for the treatment of cancer. One particular compound disclosed in WO2009/001021 is shown below.

This particular compound (known as CCT137690) is a potent and orally bioavailable inhibitor of Aurora kinases that inhibits the growth of a SW620 human colon carcinoma xenograft in vivo with concomitant biomarker modulation consistent with target engagement.26 However, the preclinical development of this compound was limited because of its narrow safety margin against hERG43 (IC50=3.0 μM)26 and its low human liver microsomal stability (86% metabolised after a 30 min incubation, unpublished data).
It is therefore an object of the present invention to provide orally bioavailable inhibitors of Aurora kinase enzyme activity are suitable for preclinical and clinical evaluation.
It is therefore an object of the present invention to provide orally bioavailable inhibitors of Aurora kinase enzyme activity that possess acceptable human microsomal stability, reduced inhibition of cytochrome P450 activity and, in the case of certain compounds, a wider therapeutic index against hERG.
FLT3 is a trans-membrane kinase that belongs to the class III receptor tyrosine kinase (RTK) family. Binding of FLT3-ligand (FL) to its receptor leads to dimerisation, autophosphorylation and subsequent activation of downstream signalling pathways37. High levels of FLT3 expression have been found in acute myeloid leukaemia (AML) blasts, and two major classes of mutations, i.e. internal-tandem duplications (ITDs) and tyrosine kinase domain (TKD) point mutations, have been identified in AML patients37,38. Internal-tandem duplications are detected in 20-25% of AML patients, and tyrosine kinase domain point mutations in 5-10% of AML patients37,38. A number of small-molecule inhibitors of FLT3 have been evaluated in clinical trials38,39.
There is, therefore, a further need for compounds that have a dual function of inhibiting both Aurora kinases and FLT3. Such compounds would be useful for the treatment of diseases and/or conditions in which Aurora and/or FLT3 are implicated, such as, for example, AML.
It is therefore a further object of the present invention to provide compounds possessing this dual activity.